Background: Psychological illness could affect the gut transmission. However, few studies have reported on the association between anxiety and depression and bowel preparation failure at colonoscopy. Bowel air bubbles have become an indispensable index to evaluate intestinal cleanliness. The aim of the present study was to investigate whether anxiety and depression are associated with the bowel air bubbles. Methods: The present study was a prospective observational study of patients who underwent colonoscopy in our hospital. Participants received the standard bowel preparation guidance, including split-dose polyethylene glycol and a low-fiber diet 1 day before colonoscopy. The primary outcome was degree of the bowel air bubble, measured by bubble scores. Univariate and multivariate logistic regression analyses were used to verify the association between anxiety and depression and bowel air bubbles. Results: A total of 304 patients were enrolled in the present study between July 2019 and January 2020; 302 of these had complete data. The mean age was 48.74±11.73 years. Fifty six of 302 patients had anxiety. Age between 45 and 60 years [odds ratio (OR): 2.09, 95% confidence interval (CI): 1.13–3.87], age >60 years (OR: 1.99, 95% CI: 1.01–3.95), and anxiety (OR: 3.85, 95% CI: 2.12–6.97) were identified as risk factors for bowel air bubbles. A bachelor degree and above (OR: 0.27, 95% CI: 0.07–0.97) were identified as protective factors for bowel air bubbles. Conclusions: Anxiety is an independent risk factor of bowel air bubbles in colonoscopy diagnosis. Medical professionals should be mindful of this prior to performing colonoscopy. © Annals of Palliative Medicine. All rights reserved.